DOPAMINE INDUCES APOPTOSIS-LIKE CELL-DEATH IN CULTURED CHICK SYMPATHETIC NEURONS - A POSSIBLE NOVEL PATHOGENETIC MECHANISM IN PARKINSONS-DISEASE

被引:209
作者
ZIV, I
MELAMED, E
NARDI, N
LURIA, D
ACHIRON, A
OFFEN, D
BARZILAI, A
机构
[1] BEILINSON MED CTR, DEPT NEUROL, IL-49100 PETAH TIQWA, ISRAEL
[2] BEILINSON MED CTR, FELSENSTEIN RES INST, IL-49100 PETAH TIQWA, ISRAEL
[3] GEORGE S WISE FAC LIFE SCI, DEPT BIOCHEM, TEL AVIV, ISRAEL
关键词
DOPAMINE; APOPTOSIS; PARKINSONS DISEASE; FLOW-CYTOMETRY; DNA DAMAGE; FREE RADICAL;
D O I
10.1016/0304-3940(94)90258-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We report that exposure of cultured, postmitotic chick-embryo sympathetic neurons, to physiological concentrations of dopamine (0.1-1 mM) for 24 h initiates a cellular death process characteristic of apoptosis (= programmed-cell-death, PCD). Dopamine caused marked morphological alterations, mainly axonal disintegration and severe shrinkage and condensation of cell bodies. Flowcytometric analysis of propidium-iodide-stained cell nuclei revealed the characteristic apoptotic nuclear fragmentation: increase in nuclear granularity and emergence of a large, distinct population of nuclei with reduced DNA content (subdiploid, apoptotic peak). These alterations were similar to changes induced by nerve growth factor (NGF) deprivation, a model of sympathetic neuronal PCD. Alterations were inhibited by the anti-oxidative agent DTT. Inappropriate, dopamine-induced activation of PCD might have a role in nigral neuronal degeneration in Parkinson's disease.
引用
收藏
页码:136 / 140
页数:5
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